PROJECT SUMMARY Prescription opioid overdoses claimed 17,087 lives in the United States in 2016, more than in any previous year. In addition, the US experiences more than 1,000 emergency department visits every day from complications from prescription opioids. These adverse outcomes reflect the US's current high prevalence of opioid prescribing. Note that about 20% of the US adults receive one or more opioid prescriptions each year. In March 2016, the Centers for Disease Control and Prevention (CDC) released national opioid prescribing guidelines for chronic non-cancer pain to address the overprescribing of opioids. The guidelines include a specific guideline for acute pain recommending that for most acute pain, a prescription of 3 days of outpatient opioid pain reliever (OPR) should be sufficient and more than 7 days would rarely be needed. The CDC guidelines include a call to evaluate the effect of implementation of the guidelines. In June 2017, North Carolina's STrengthen Opioid Misuse Prevention (STOP) act mandated CDC guidelines for acute and post- surgical pain, effective January 1 2018. This act legislatively limited first outpatient OPR prescriptions to a) ? 5 days for acute pain, and b) ? 7 days for post-surgical pain. The overall goal of this study is to conduct an impact and process evaluation of North Carolina's legislative mandate of the CDC opioid prescribing guidelines for acute and post-surgical pain. While five other states have also adopted similar laws, North Carolina (NC) provides an optimal setting for examining the effect of this opioid prescribing guideline because NC's STOP act prescribing mandate is most closely aligned with the CDC opioid prescribing guideline for acute pain. In this study, we will used mixed methods to conduct 1) a quasi-experimental impact evaluation and 2) a qualitative process evaluation of the implementation of state mandated CDC opioid prescribing guideline for acute and post-surgical pain in NC. We will use existing electronic health records data from three large integrated healthcare delivery systems in NC and Tennessee (TN). We will link NC and TN electronic health records from 2010 to 2020 to each state's prescription drug monitoring program and death records. The linked data from >2 million acute and post-surgical pain patients who received opioids for pain control will be used in a comparative interrupted time series analysis. Essentially, we will conduct 2-group pre/post policy evaluation in which one state (NC) will serve as pre/post intervention and the other state (TN) will serve as control (TN does not have a similar policy). We will use latent class growth analysis to model heterogeneity in physicians' opioid prescribing patterns before and after implementation of the state-mandated CDC opioid prescribing guideline. We will also conduct a process evaluation to understand the multi-system level resources, strategies, and partnerships that may aid the implementation of the guidelines. Using Wandermann's interactive systems framework, the results from the impact and process evaluations will be used to develop recommendations to guide the legislative implementation of other CDC opioid prescribing guidelines in other states.